Boston, US-based start-up Cerevance, is looking inside the brain to identify novel protein targets for diseases such as Parkinson’s and Alzheimer’s.
The approach, which is termed NETSseq, extracts nuclei from brain cells and sorts them using antibodies and RNA probes that identify proteins specific to different cell types. The cells’ RNA is sequenced to pinpoint the proteins they are making and in what quantities. The approach was invented by Nat Heintz and Xiao Xu at Rockefeller University. They used the method in a study of 16 post-mortem brains which revealed gender differences and cell-specific molecular responses to ageing. The company’s technology for isolating discrete cells types and sequencing RNA has since been scaled up.
Brad Margus ceo of Cerevance said ‘The idea is to look at each cell by itself, without any noise, and see which genes are expressed in healthy donors and how gene expression changes when people have [central nervous system] disease.’ Proteins linked to a diseased condition in discrete populations of cells can then be targeted. The improved specificity should reduce drug side effects, which are often the result of non-target cells being hit by a therapeutic.
The company’s lead therapeutic targets entered entered Phase 2 trials in Parkinson’s disease patients in the US during September 2019. The company also hopes to discover what marks out specific cell types that die early in brain diseases, such as those cells in the hippocampus that are vulnerable in people with Alzheimer’s.
Cerevance is in talks with both big pharma and other biotechs about future partnerships.
For further details visit this month’s issue of Chemistry and Industry.